Device for cleaning pipette probes or stirrers

ABSTRACT

The invention concerns a device for cleaning pipette needles or stirrers, the device comprising a trough which holds cleaning fluid and whose lower region has a fluid duct for filling and/or emptying purposes and whose upper region has at least one feed pipe which leads into at least one nozzle directed into the trough interior. Advantageously, the device has a cylindrical trough and in insert with nozzles which is screwed into the trough. The invention further concerns a method of cleaning pipette needles or stirrers, the material to be washed being introduced into the trough interior and sprayed with a washing fluid. The device can also be used to flush the interior of a pipette needle.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a divisional of U.S. Patent Application No. 09/142,261, filedDec. 15, 1998, now U.S. Pat. No. 6,422,248, which is the U.S. NationalStage of PCT/EP97/01311, filed Mar. 15, 1997, which in turn claimspriority to DE 196 10 607.9, filed Mar. 18, 1996. The contents of allapplications are incorporated herein in their entirety by reference.

BACKGROUND OF THE INVENTION

The present invention is used in the field of automated analysis whereliquids are pipetted with pipettes and fluids are stirred with stirrersas necessary.

The present invention provides a device for cleaning pipette probes orstirrers, comprising

-   -   a cavity that holds cleaning fluid and whose lower region has a        fluid duct for filling and/or emptying the cavity, and    -   at least one inlet tube which empties into at least one nozzle        directed toward the interior of the cavity.

When sample fluids such as blood or urine are analyzed, they must bepipetted into containers along with any necessary wash fluids, reagents,etc. The pipette must be rinsed between pipettings to avoid carryoverbetween consecutive samples or reagents. If fluids must be mixed inautomated analyzers, this is usually performed using stirrers that arelowered into the sample fluid. The stirrer must be cleaned between eachstep in the mixing procedure to avoid carryover of the material to bemixed by the stirrer. Examples of materials to be mixed include fluidsand suspensions, such as magnetic microparticles in fluid.

Washing device for pipettes and stirrers are known from the prior art inwhich the devices to be washed are inserted into a cavity filled withwash fluid and the wash fluid is replaced after one or more wash steps.The fluid is usually replaced by removing the fluid through a fluid ductusing suction.

A device for washing pipettes is described in European patentapplication 0 661 542 in which the pipette is inserted into a tube thatsurrounds the pipette at a distance of 1 mm or less. Fluid is injectedinto the tube to wash the pipette.

Devices with a cavity known in the prior art have the disadvantage inthat the fluid is injected into and emptied from the cavity through thesame fluid duct, making it inevitable that used and fresh wash fluid aremixed. Moreover, these devices have the disadvantage that they operateaccording to a dilution principle. In other words, the fluid thatadheres to the pipette is diluted with the wash fluid. Even after thepipette is removed from the cavity. therefore, fluid which iscontaminated to a certain extent is still adhered to it. Although thisproblem is avoided with the device described in EP-A-0 661 542, thisdevice is limited to a certain type of pipette because the duct isdesigned to accommodate a pipette of a certain diameter. This washdevice therefore cannot be used with different types of pipettes or forpipettes and stirrers interchangeably.

BRIEF DESCRIPTION OF THE INVENTION

The task of the present invention was to provide a device for cleaningpipettes or stirrers very effectively that can be used to clean variousobjects such as different types of pipettes or stirrers. A further taskof the invention was to provide a device with a simple mechanical designthat can be integrated into existing automated analyzers or automatedanalyzer concepts.

DETAILED DESCRIPTION OF THE INVENTION

A device for cleaning pipettes and stirrers provided by the inventionhas a cavity for holding cleaning fluid. The cavity is preferably shapedlike a hollow cylinder with an internal diameter of between 0.7 and 3.5cm. The cylinder can also have a base that is not round. The area of thecylinder that is filled with wash fluid is about 10 cm high, although itcan vary up or down considerably, depending on the application. Thecavity can be manufactured from a number of materials such as metals orplastics, with plastics being the preferred material. The device ispreferably designed so that it can be securely attached to a base in anupright position. Moreover, the device has a number of openings.

The lower region of the cavity has an opening that serves as a fluidduct for filling and/or emptying the cavity. This opening is preferablylocated at the lowest point possible inside the cavity to ensure thatused wash fluid can be removed from the cavity as completely aspossible. This can be accomplished, for instance, if the bottom of thecavity is bent or slanted.

The upper region of the cavity has one or more openings for fluid ductsthat empty into one or more nozzles. The one or more nozzles aredirected toward the interior of the cavity and serve to spray a pipetteprobe or stirrer that is inserted into the cavity. Each of the nozzlesis preferably positioned so that the fluid stream ejected from it pointsdownward at a 20 to 70°—and preferably approximately 45°—angle fromhorizontal. If the device contains numerous nozzles, it is alsoadvantageous for them to be positioned in such a way that the fluidstreams meet at one point, preferably in the longitudinal axis of thecavity. In an especially preferred design, the nozzles are located in aninsert that can be screwed into the cavity. A groove runs around theoutside of the metal insert that contains holes for the nozzles. Whenthe metal insert is screwed into the cavity, an intermediate space formsin the groove between the cavity and the insert that is filled with washfluid through one or more inlet tubes. In an advantageous design, twoinlet tubes are used that are positioned on opposite sides of thecavity. The insert that is screwed into the cavity can be manufacturedfrom a number of materials such as plastics or metals. Metals arepreferred, especially stainless steels such as 1.4435 and 1.4305 (olddesignations: V2A and V4A), that are resistant to cleaning fluids.

It is also advantageous to the function of the device provided by theinvention if the upper region of the cavity contains at least oneadditional opening for another fluid duct, below the nozzles. The cavitycan be filled With fresh wash fluid through this fluid duct. This fluidduct can also be used as an outlet for overflowing liquid or to emptyfluids using suction to keep the column of water in the cavity at adefined level. This is especially advantageous if the fluid leaving thenozzles cannot be controlled exactly and the fluid level can thereforenot be controlled simply by any other means. It is advantageous to knowthe fluid level in the cavity in advance to eliminate the need toperform liquid level detection, and to avoid inserting the pipette intothe fluid farther than desired. This also makes it easier to standardizethe wash processes.

The invention also provides a system consisting of a pipette probeattached to a drive arm or a stirrer attached to a drive arm, and adevice for cleaning pipette probes or stirrers according to theinvention. “Item to be bashed” in the context of this application refersto both pipette probes and stirrers. Pipette probes or stirrers attachedto a drive arm are commonplace in automated analyzers described in theprior art, so drive arms and their control mechanisms will not bedescribed here in detail. For the present invention, however, it isimportant that a central control unit be provided that coordinates andregulates the movement of the drive arms and the control of the fluidstreams and pumps. The drive arm must move the pipette probe or thestirrer over the opening in the cavity and lower the item to be washedinto the cavity. The drive arm must therefore be capable of performing arotational and translational movement in the vertical planes ortranslational movements in at least two spacial directions.

The invention also provides a method for cleaning pipette probes orstirrers using a device according to the invention in which the pipetteprobe or stirrer is inserted into the cavity and sprayed with wash fluidby at least one nozzle. It is favorable to lift the item to be washed toa height at which the area that is wetted with fluid during pipetting orstirring is located entirely below the level of the nozzles. On theother hand, it is unfavorable if an area of the item to be washed issprayed that is larger than the one described above, because there is arisk of fluid being sprayed on electrical contacts or the like, or ofdecreasing the effectiveness of the washing procedure. It is especiallyfavorable if the upper edge of the area of the item to be washeddescribed above is located 5 to 15 mm below the level of the nozzle. Itis advantageous for the spraying to take place while the item to bewashed is lifted out of the cavity. The item to be washed can also beinserted into a wash fluid contained in the cavity. The purpose is tosoften any deposits or caked-on substances from the item to be washedand remove them by spraying them with fluid from the nozzles. The itemto be washed is cleaned with fresh wash fluid in the spraying step inorder to prevent contaminating wash fluid from adhering to the surfaceof the item to be washed after the cleaning process is over. As aresult, the wash station fills with this wash fluid. When cleaningpipette probes, it is also an advantage to rinse the inside of theprobes in such a way that the probe is dipped into the wash fluid in thecavity and wash fluid is directed through it. Dipping the pipette probeinto the wash fluid prevents the formation of an aerosol and evenfacilitates cleaning by causing fluid to swirl on the outside of theprobe.

It is advantageous for the pipette probe to be dipped into the washfluid in the cavity and removed at a speed of less than 14 cm/sec toensure that all fluid covering the probe falls off without formingdroplets. Once the pipette probe has left the fluid it can be moved at ahigher rate of speed.

The processes for washing a pipette probe described above apply to boththe inside and outside of the probe. It is also possible, of course, towash just the inside or outside of the probe. It is especiallyadvantageous to rinse the outside of the pipette between the individualuptake steps when drawing up two or more different fluids into the samepipette probe in order to prevent or at least reduce carryover. This isespecially advantageous when analytical tests are performed withreagents that can also be detected as analytes. In a case like this, thereagent could be carried over from the first test into the sample andthen lead to a false-positive test result in a subsequent test of thissample. When drawing up various fluids into one pipette probe, it hasproven effective to draw up a separating fluid or a separating airbubble into the pipette probe after drawing up a fluid (e.g., reagent)and only then to draw up another fluid (e.g., reagent or sample).

Wash fluids (also called cleaning fluids) according to the inventionrefer to the fluids and mixtures commonly used with automated analyzers,e.g., aqueous solutions to which detergents, salts, preservatives, andpossibly solubilizers have been added.

BRIEF DESCRIPTION OF THE FIGS.

A device according to the invention is described in greater detail usingthe figures below.

FIG. 1: Cross section of a device for cleaning pipette probes/stirrers

FIG. 2: Outside view of the device

FIGS. 3( a) to 3(i): Cleaning steps for a pipette probe

FIGS. 4( a) to 4(g): Cleaning steps for a stirrer

FIG. 1 shows a cross section parallel to the longitudinal axis of thecleaning device according to the invention. The device (1) has aplatform (2) on the bottom with which the device can be attached to aground plate. The device is manufactured via injection molding with PPS(polyphenylene sulfide). The inside of the device is cylindrical inshape and an initial fluid duct enters the device through the bottom ofthe cylinder. A screw (4) is located on the outside of the device, oneend of which is screwed into the device and the other end of which isoutfitted with a connection for a tube.

The upper region of the device has two openings on opposite sides of thedevice into which flanges (5) are screwed. Tubes (6) that carry washfluid are located inside the flanges (5).

The upper end of the device also has internal threads (7) into which thesteel insert (20) is screwed. Accordingly, the insert (20) has externalthreads (21) in its lower region. A ring-shaped groove (22) is locatedon the outside of the insert above this thread, and runs all the wayaround the circumference. Together with the device (1), the groove (22)forms a duct for the wash fluid ejected through the tubes (6). Thegroove (22) contains holes (23) that serve as nozzles. The device shownin FIG. 1 has six of these holes (23) that are positioned so that thefluid ejected through them meets the cylindrical axis (11) formed by thedevice. The fluid ejected through the nozzles points downward at a 45°angle from horizontal. The device has two gaskets (24, 25) to seal offthe fluid duct located between the device and the insert (20).

The device shown in FIG. 1 also has two openings (8) on opposite sidesof the device that are located below the nozzles (23) but above theopening (3). Screws (9) are screwed into these openings and connected totubes (10). The tubes (10) are connected to a suction device (not shown)to ensure that the fluid level in the cavity does not rise above thelevel of the openings (8).

FIG. 2 shows a side view of the cleaning device according to theinvention. The device (1) and screws (4, 6, and 9) are clearly visiblein this drawing. The insert (20) that is screwed into the deviceprojects out of the top of the device. The upper edge of the insert hasa flange (26) with a rough-milled surface that facilitates handling whenscrewing or unscrewing the insert (20). A device according to theinvention with an insert screwed into place has the advantage that it iseasier to clean when the insert is removed.

FIG. 3 shows the cleaning steps for a pipette probe, also called adispensing probe. In step (a), the dispensing probe is moved over thecleaning device according to the invention (labelled WD1 in the figure).At this point, fluid from the previous cleaning cycle is already locatedin the cavity of the cleaning device. In step (b), the pipetting probe(labelled DN) is lowered to the surface of the liquid using electronicliquid level detection (LLD). In step (c), the fill level detected withliquid level detection is checked. The fluid column is then lowered inthe cavity (step (d)) and the pipette probe is lowered to the fluidcolumn, which is now lower (step (e)). Using this procedure, theinjecting and emptying function of the system can be checked, and thepresence of fluid in the cavity can be monitored. The fluid column islowered completely in step (f) and the pipette probe is lowered into thecleaning device to the point where the probe tip enters a tapered regionof the cleaning device (see step (g)). The inside of the pipette probeis now flushed with fresh wash fluid. Since the pipette tip ispositioned in the low, tapered region and fluid is removed through thefluid duct on the bottom at this point, the wash fluid exiting thecleaning device is prevented from forming an aerosol, and the upperregion of the wash station is prevented from being contaminated withthis wash fluid.

After this internal wash step, the pipette is positioned as shown instep (h) so that the pipette tip is washed with the confluence of washfluid streams. The pipette can be located above or below the surface ofthe column of wash fluid at this point. The cavity fills with wash fluidwhen the dispensing probe is sprayed. After washing, the pipette isinserted slightly into the wash fluid (see step (i)). This position canbe identical to the position in which fluid falls off of the probe. Theinterior of the pipette is now rinsed again when fluid is injectedthrough it into the cavity (see step (i)). After this rinse step, thepipette is moved into a defined position in which fluid falls off of theprobe k), if necessary. The pipette is then slowly removed from the washfluid (step (k)). After the pipette is removed from the cleaning device,it returns to its home position (see step (l)).

If substance to be dispensed is located in the dispensing probe, onlythe exterior of the probe is rinsed. This cycle begins with the homeposition (a), skips steps (b) through (g) and continues with (h). Therinsing takes place as described in (h) (the cavity is still filled asshown in (a)). Step (i) is skipped, and the cycle ends with steps (j),(k), and (l). In this procedure, it is advantageous for a small quantityof fluid and/or an air bubble to be drawn up at the end or after step(h). It is especially favorable if fluid is drawn into the dispensingprobe from a drop that remains on the tip of the dispensing probe afterspraying. It is also possible to draw fluid up immediately from theclean surface of the fluid in the wash station.

An air bubble is drawn up at the end of step (k) or (l). This quantityof fluid, which serves as a separator, is usually less than 5 μl, and ispreferably between 1 and 3 μl. The fluid is preferably drawn up onlyafter a reagent drawing up and before a sample drawing up. The samesequence applies for drawing up an air bubble.

FIG. 4 shows the cleaning steps for a stirrer. The home position of thecleaning device with the stirrer is shown in FIG. 4 a. A water column isformed and the stirrer is dipped into the wash fluid (FIGS. 4 a, c, andd). The stirrer is cleaned by turning it, the column of water lowered(FIG. 4 c). The stirrer is rotated quickly to spin off any fluid stilladhering to it (FIG. 4F). The stirrer is then removed from the cleaningdevice (FIG. 4 f).

Legend  1 Device  2 Platform  3 Fluid duct  4 Screw  5 Screw  6 Tube  7Internal thread  8 Hole  9 Screw 10 Tube 20 Insert 21 External thread 22Ring-shaped groove 23 Bore holes 24, 25 Gaskets 26 Rough-milled flange

1. A method of washing an outside and a tip portion of a pipette probebetween the uptake of at least two fluids such that a first fluid insidethe pipette probe does not contaminate a reservoir holding a secondfluid, the method comprising: uptaking the first fluid into the pipetteprobe; inserting the pipette probe into an interior cavity of anapparatus containing a cavity for holding wash fluid that has a fluidduct in its lower region for filling and/or emptying the cavity, atleast one inlet tube in an upper region that is connected to at leastone nozzle that is directed towards the interior of the cavity, and atleast one discharge duct that enters the interior of the cavity abovethe fluid duct and below the inlet tube; spraying the outside of thepipette probe with a wash fluid ejected through at least one nozzle;moving the pipette probe to a position where the wash fluid is wiped offthe probe; drawing a separating fluid or a separating air bubble intothe pipette probe, wherein the separating fluid is one selected from agroup consisting of the wash fluid in the interior of the cavity and aseparating fluid in a separate reservoir; inserting the pipette probeinto the reservoir containing the second fluid; and uptaking the secondfluid into the pipette probe after the separating fluid or air bubble isdrawn into the pipette probe.
 2. Method according to claim 1 in which aseparating fluid or an air bubble of a volume equal to only a portion ofthe pipette probe tip is drawn up.
 3. Method for cleaning pipette probesbetween the uptake of at least two fluids according to claim 1, whereinboth a separating fluid and an air bubble are drawn into the pipetteprobe after the pipette is moved to a position where the wash fluid iswiped off the probe and before a second fluid is drawn into the pipetteprobe after the separating fluid.
 4. Method according to claim 3 inwhich a separating fluid and an air bubble of a volume equal to only aportion of the pipette probe tip are drawn up.
 5. Method according toclaim 1 in which the separating fluid is wash fluid, which is drawn froma droplet that remains on the pipette probe after the spraying step. 6.Method according to claim 1 further comprising inserting the pipetteprobe into a reservoir containing a separating fluid after moving thepipette to a position where the wash fluid is wiped off the probe, fromwhich reservoir, the separating fluid is drawn.
 7. The method accordingto claim 1, wherein the wash fluid is wiped off the pipette probe byinserting the pipette probe into the wash fluid contained in the cavityand then slowly removing the pipette probe from the wash fluid at aspeed sufficiently slow to ensure that all the wash fluid covering thepipette probe is wiped off and does not form droplets on the pipetteprobe.
 8. The method according to claim 1, further comprising leadingwash fluid through the pipette probe while it is immersed in the washfluid in order to wash the interior of the probe.
 9. A method of washingan outside and a tip portion of a pipette probe between the uptake of atleast two fluids such that a first fluid inside the pipette probe doesnot contaminate a reservoir holding a second fluid, the methodcomprising: drawing the first fluid into the pipette probe; insertingthe pipette probe into an interior cavity of an apparatus containing acavity for holding wash fluid that has a fluid duct in its lower regionfor filling and/or emptying the cavity, at least one inlet tube in anupper region that is connected to at least one nozzle that is directedtowards the interior of the cavity, and at least one discharge duct thatenters the interior of the cavity above the fluid duct and below theinlet tube; spraying the outside of the pipette probe with a wash fluidejected through at least one nozzle; during the spraying step, drawingthe wash fluid into the pipette probe as a separating fluid, wherein thewash fluid is either drawn from a drop of wash fluid that remains on thetip of the pipette probe or from a clean surface of the wash fluid inthe interior cavity of the apparatus; moving the pipette probe to aposition where the wash fluid is wiped off the probe; inserting thepipette probe into the reservoir containing the second fluid; anddrawing the second fluid into the pipette probe.
 10. Method according toclaim 9, in which a of separating fluid of a volume equal to only aportion of the pipette probe tip is drawn up.
 11. The method accordingto claim 9, wherein the wash fluid is wiped off the pipette probe byinserting the pipette probe into the wash fluid contained in the cavityand then slowly removing the pipette probe from the wash fluid at aspeed sufficiently slow to ensure that all the wash fluid covering thepipette probe is wiped off and does not form droplets on the pipetteprobe.
 12. The method according to claim 9, further comprising leadingwash fluid through the pipette probe while it is immersed in the washfluid in order to wash the interior of the probe.
 13. A method ofwashing an outside and a tip portion of a pipette probe between theuptake of at least two fluids such that a first fluid inside the pipetteprobe does not contaminate a reservoir holding a second fluid, themethod comprising: uptaking the first fluid into the pipette probe;drawing a separating fluid or a separating air bubble into the pipetteprobe; inserting the pipette probe into an interior cavity of anapparatus containing a cavity for holding wash fluid that has a fluidduct in its lower region for filling and/or emptying the cavity, atleast one inlet tube in an upper region that is connected to at leastone nozzle that is directed towards the interior of the cavity, and atleast one discharge duct that enters the interior of the cavity abovethe fluid duct and below the inlet tube; spraying the outside of thepipette probe with a wash fluid ejected through at least one nozzle;moving the pipette probe to a position where the wash fluid is wiped offthe probe; inserting the pipette probe into the reservoir containing thesecond fluid; and uptaking the second fluid into the pipette probe afterthe separating fluid or air bubble is drawn into the pipette probe. 14.The method according to claim 13, wherein both a separating fluid and anair bubble are drawn into the pipette probe before the probe is insertedinto the interior cavity of the apparatus.
 15. The method according toclaim 13, wherein an air bubble is drawn into the pipette before theprobe is inserted into the interior cavity of the apparatus and furthercomprising drawing a separating fluid into the pipette probe beforeuptaking the second fluid into the pipette probe.
 16. The methodaccording to claim 13, wherein a separating fluid is drawn into thepipette probe before the probe is inserted into the interior cavity ofthe apparatus and further comprising drawing an air bubble into thepipette probe before uptaking the second fluid into the pipette probe.17. The method according to claim 13, wherein the wash fluid is wipedoff the probe by inserting the pipette probe into the wash fluidcontained in the cavity and then slowly removing the pipette probe fromthe wash fluid at a speed sufficiently slow to ensure that all the washfluid covering the pipette probe is wiped off and does not form dropletson the pipette probe.
 18. A method of washing an outside and a tipportion of a pipette probe between the uptake of at least two fluidssuch that a first fluid inside the pipette probe does not contaminate areservoir holding a second fluid, the method comprising: uptaking thefirst fluid into the pipette probe; inserting the pipette probe into aninterior cavity of an apparatus containing a cavity for holding washfluid that has a fluid duct in its lower region for filling and/oremptying the cavity, at least one inlet tube in an upper region that isconnected to at least one nozzle that is directed towards the interiorof the cavity, and at least one discharge duct that enters the interiorof the cavity above the fluid duct and below the inlet tube; sprayingthe outside of the pipette probe with a wash fluid ejected through atleast one nozzle; inserting the pipette probe into a clean, top layer ofwash fluid contained in the interior cavity of the apparatus; drawingclean wash fluid into the pipette probe as a separating fluid; movingthe pipette probe to a position where the wash fluid falls off theprobe; inserting the pipette probe into the reservoir containing thesecond fluid; and uptaking the second fluid into the pipette probe afterthe separating fluid or separating air bubble is drawn into the pipetteprobe.
 19. A method of washing an outside and a tip portion of a pipetteprobe between the uptake of at least two fluids such that a first fluidinside the pipette probe does not contaminate a reservoir holding asecond fluid, the method comprising: uptaking the first fluid into thepipette probe; inserting the pipette probe into an interior cavity of anapparatus containing a cavity for holding wash fluid that has a fluidduct in its lower region for filling and/or emptying the cavity, atleast one inlet tube in an upper region that is connected to at leastone nozzle that is directed towards the interior of the cavity, and atleast one discharge duct that enters the interior of the cavity abovethe fluid duct and below the inlet tube; inserting the pipette probeinto a clean, top layer of wash fluid contained in the interior cavityof the apparatus; drawing clean wash fluid into the pipette probe as aseparating fluid; spraying the outside of the pipette probe with a washfluid ejected through at least one nozzle; moving the pipette probe to aposition where the wash fluid is wiped off the probe; inserting thepipette probe into the reservoir containing the second fluid; anduptaking the second fluid into the pipette probe after the separatingfluid or air bubble is drawn into the pipette probe.
 20. The methodaccording to claim 19, wherein the wash fluid is wiped off the pipetteprobe by inserting the pipette probe into the wash fluid contained inthe cavity and then slowly removing the pipette probe from the washfluid at a speed sufficiently slow to ensure that all the wash fluidcovering the pipette probe is wiped off and does not form droplets onthe pipette probe.